Interleukin-1 increases tumor cell adhesion to endothelial cells through an RGD dependent mechanism: in vitro and in vivo studies.
The effects of human recombinant interleukin-1 alpha and beta (rIL-1 alpha; rIL-1 beta) on the adhesion of human A549 lung carcinoma cells and M6 melanoma cells (TC) to human endothelial cells (HECs) in vitro were studied, and on TC/lung entrapment in vivo. In vitro, there was a significant increase in TC/HEC adhesion to HECs pretreated for 4 h with rIL-1 alpha or rIL-1 beta. The effects of rIL-1 alpha and beta on TC/HEC adhesion were time dependent and reached a plateau within 4-6 h. TC/HEC adhesion was not blocked when measured in the presence of antibodies to either fibronectin, glycoprotein IIb/IIIa, anti-ICAM, or anti-LFA. However, enhanced TC/HEC adhesion was completely blocked in the presence of the peptide, GRGDS. In vivo, pretreatment of nude mice for 4 h with rIL-1 alpha (given i.p. before i.v. injection of TCs) enhanced TC retention in the lung 24 h later. Our data demonstrate that IL-1 enhances TC adhesion to the vascular surface both in vitro and in vivo, suggesting that IL-1 can facilitate the metastatic process.
Lauri
D
D
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Bertomeu
M C
MC
Orr
F W
FW
Bastida
E
E
Sauder
D
D
Buchanan
M R
MR
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms; D008545:Melanoma; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009368:Neoplasm Transplantation; D011652:Pulmonary Circulation; D011994:Recombinant Proteins / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D007375:Interleukin-1; D011994:Recombinant Proteins